Bacterial vaginosis (BV) is associated with an increased volume of vaginal discharge having a foul, fishy odor. Vaginal pH is elevated from the normal range (pH 3-4) to values greater than or equal to about pH 4.7. The odor and elevated pH are caused by a high level of amines, most notably trimethylamine, in the vagina. These amines are volatilized when the pH is raised, for example, as with addition of KOH or interaction with semen. The vaginal discharge is homogenous in appearance as opposed to the flocculent discharge seen in candidiasis. In contrast to candidiasis and trichomoniasis, itching generally is not associated with BV. A microscopic examination of a wet mount of the vaginal discharge in BV reveals an absence of polymorphonuclear leukocytes (PMNs). In contrast, the presence of many PMNs in a vaginal discharge is indicative of trichomoniasis, gonorrhea, or chlamydial cervicitis.
Typically, a clinical diagnosis of BV is made if three or more of the following four clinical criteria are present: (1) a homogenous discharge; (2) a pH value greater than or equal to about 4.7; (3) a “fishy” amine odor upon the addition of 10% KOH to discharge; (4) presence of epithelial clue cells in an amount greater than or equal to about 20% of vaginal epithelial cells.
Vulvovaginal candidiasis is a relatively common form of yeast infection involving an over-proliferation of Candida albicans and related species in the vulvovaginal region. The disease can be treated with anti-fungal compositions such as miconazole nitrate. One common regimen for treating vulvovaginal candidiasis with miconazole nitrate comprises repeated intra-vaginal application of a cream containing miconazole nitrate over a period of several days to about a week.
U.S. Pat. No. 5,536,743 to Borgman describes a pH buffered, aqueous gel formulation of the antimicrobial agent metronidazole for treatment of BV. While providing an effective treatment for BV, metronidazole gel has been reported to have some undesirable side effects in some patients, such as yeast vaginitis following therapy, vulvovaginal irritation, and gastrointestinal discomfort. In addition, metronidazole can have adverse interactions with alcohol ingested by the patient.
Benzydamine hydrochloride (B—HCl) is a non-steroidal anti-inflammatory drug (NSAID) that is commercially available in Europe and other countries for topical application. B—HCl has the dual advantage of being an analgesic as well as having anti-microbial activity. A cream formulation of B—HCl, available under the trade name TANTUM ROSA® from Angelini Pharmaceuticals, Rome, Italy, has been utilized in a number of countries as a topical treatment for vaginal infections. The cream formulation, however, has a disadvantage of being difficult to administer intravaginally, remains in contact with the vaginal tissue for a relatively short period of time, and provides relatively rapid delivery of the active agent (B—HCl). These factors lead to a necessity for multiple applications of the cream formulation over a six to ten day period in order to treat a vaginal infection.
A desirable treatment for vaginal infections would be a sustained-release gel composition for intravaginal administration that delivers the active agent over an extended period of time and remains in contact with the vaginal tissue for a time period sufficient for substantially all of the active agent to be released. The present invention provides such a desirable treatment in the form of an aqueous polyoxyalkylene block copolymer gel formulation of B—HCl.